Title: Carotid artery stenting in patients with coexistent carotid and coronary artery disease
Abstract: Atherosclerotic disease, as a systemic process, affects all arteries to varying degrees. In particular, coexistent carotid and coronary artery diseases are common; Management of such patients has been a point of continuing controversy.1 Current American Heart Association (AHA) guidelines2 recommend carotid endarterectomy (CEA) in symptomatic patients with carotid artery stenosis of 50%-99% and in asymptomatic patients with stenosis of 60%-99%. Carotid artery stenting (CAS) has become a reasonable alternative to CEA, particularly in patients at high risk for CEA.3-6 We sought to assess feasibility, safety and midterm outcome of carotid artery stenting in patients with coexisting symptomatic coronary disease and carotid artery stenosis. METHODS Patients Between May 1998 and September 2006, CAS was performed for 56 patients with coexisting symptomatic coronary artery disease and carotid artery disease at our institute. All the patients were admitted for their angina symptoms within one month. If ultrasound duplex found carotid stenosis more than 70%, angiography was performed for both carotid and coronary arteries at the same time. When angiography found carotid artery stenosis more than 70% (NASCET criteria 6), CAS was carried out whether neurological symptoms were present or not. Patients were excluded if any of the following exsited: inability to give informed consent; presence of severe disability due to previous stroke or dementia; presence of an intracranial tumor or arteriovenous malformation; presence of intracranial arterial stenosis that exceeded the severity of extracranial stenosis; or if the predicted life expectancy was less than 3 years due to terminal disease state. Interventional procedures During the procedures accessed via femoral artery percutaneously, a 7F × 90 cm shuttle anti-kinking sheath (Cook USA) was inserted to target side common carotid artery. After a 0.3556-mm (0.014-inch) or 0.4572-mm (0.018-inch) wire (BMW, Guidant USA or Roadrunner Cook) crossed the target lesion, pre-dilatation was done by 4 mm × 20 mm balloon (Worldpass, Cordis USA) or 5 mm×20 mm balloon (Powerflex, Cordis) in 607.95 kPa (6 atmospheres). During the first several years, CAS was performed without emboli protection device (EPD) in 12 patients, while in the others (n=44) EPD was used. EPDs used in these patients included Angioguard (Cordis, Johnson & Johnson, USA) or Filterwire (BSC, USA). The self-expended stent (Wallstent, BSC) or SMART/Precise (Cordis, Johnson & Johnson) was deployed to cover the lesion post-dilatation and a 5-6.0 mm×20 mm balloon was used for post-dilatation with low pressure (≤ 607.95 kPa). Final carotid and intracranial angiography was performed to evaluate the angiographic result before the procedure was finished. During the procedure, pacing wire and intravenous medication were applied according to the patient's clinical situation. Concomitant therapy All patients received aspirin (100 mg/d) and clopidogrel (75 mg/d) or ticlopidine (500 mg/d) 2 days before intervention, and continued to take clopidogrel (75 mg/d) or ticlopidine 500 mg/d for at least 2 weeks and then 250 mg/d for 2 weeks after CAS, and aspirin 100 mg/d at the same time. Data collection and follow up All clinical, angiographic, and stenting data were recorded prospectively. Clinical endpoints were any transient ischemic event, minor or major stroke during hospital stay, myocardial infarction defined either as the development of new Q-waves on the ECG or as elevated CK-MB levels to more than twice the normal value, functional class defined according to the Canadian Cardiovascular Society (CCS) classification for angina pectoris symptoms before and after the procedure, and, finally, the occurrence of clinical events and repeat intervention during follow-up. Angiographic endpoints were angiographic success rate, defined as a residual stenosis of ≤ 30% in all targeted vessels, and the occurrence of restenosis of ≥50% determined by Doppler ultrasound (carotid artery) or angiography (carotid artery and coronary arteries) during follow-up. The study was approved by our institutional review board. Follow up visits were accomplished at 3, 6, and 12 months and stress tests (treadmill test or nuclear stress test) at 6 and 12 months. Follow-up surveillance of the implanted stent was performed by Doppler ultrasonography at 6 and 12 months. Continuous variables are presented as means ±standard deviation (SD), while categorical variables as number (percentage). RESULTS Patient characteristics Total 56 patients (35 male and 21 female) were enrolled in this study, with mean age of (69 ±5) (range 54 to 78) years. Thirty-five patients (62.5%) had symptoms attributable to the treated artery before the procedure, ten (17.9%) had stroke and 25 (44.6%) had transient ischemic attack (TIA). Sixteen patients (28.6%) were diabetic and 32 (53.2%) hypertensive. Fourteen patients (25.0%) had previous myocardial infarction. Double vessel coronary disease was found in 21 patients (37.5%) and treble vessel coronary disease in 13 patients (23.2%). Staged or combined coronary intervention was performed in 25 patients (44.6%), and staged coronary artery bypass surgery was performed in 3 patients (5.4%), while medication in the other patients. Procedural characteristics and complications The technical success rate was 100%. No procedure related symptoms of intracranial emboli symptoms and cardiac events were found in any of the patients. Mean lesion length was (12 ± 4) mm. Mean angiographic stenosis was reduced from (83±6)% to (7±2)%. The mean stent diameter was (8.5±1.3) mm and the mean stent length was (22±8) mm. Fifteen patients had bradicardia and one of them had hypotension, all of which recovered within minutes after activating pacing wire or giving proper medication (atropine and/or aramine) intravenously. Unfortunately, one patient was complicated with a contralateral cerebral hemorrhage during the procedure and died 4 days later. Follow-up results During the mean follow-up of (14±7) (3 to 40) months, no deaths or neurological events were found, angiography and/or duplex sonography showed asymptomatic restenosis in 2 cases (3.5%). DISCUSSION This study demonstrated the safety and favorable follow-up results of CAS in patients with coexisting coronary and carotid occlusive disease. Endovascular intervention combined with or staged CAS and percutaneous coronary intervention (PCI), seemed to be a treatment option in the population studied. Carotid and coronary artery stenosis frequently coexists as part of the systemic atherosclerotic process. Incidence of combined disease with greater than 75% stenosis affecting at least one carotid artery in recent literature has varied from 1.7% to 12%.1 The incidences of stenosis greater than 50% in reports have been as high as 22%.7 Although a significant amount of information is currently available with regard to the dilemma of myocardial revascularisation in the presence of carotid arterial disease, the choice of treatment for patients who present with severe carotid artery stenosis is still a matter of debate. Carotid stenting offers the potential of non-surgical treatment of carotid bifurcation stenoses with possibly lower morbidity than surgery in those patients in high surgical risk categories.8 The results of our study showed several potential advantages of CAS over CEA. Patients were not required to discontinue anticoagulation (heparin) therapy before undergoing CAS. General anesthesia was not required and, consequently, less stress was placed on the cardiovascular system. The endovascular approach allows treatment of tandem lesions and stenoses in other vessels. Frequent neurological assessments allow the recognition of embolic events. Last, intra-arterial thrombolysis can easily be used to salvage a thromboembolic complication. In China, the operators are stepping on learning curve in CAS, and several CAS cases series have been reported in recent years.9,10 There are few reports about CAS in patients with coexistent carotid and coronary artery disease. In our institution, good acute and long-term results were achieved in 56 cases. Our data support CAS with or without PCI can be one of safe and feasible treatment options in such patients. Unfortunately, one procedure was complicated by a fatal cerebral hemorrhage which occurred in contralateral side of CAS. This patient's high blood pressure (200/100 mmHg) during the stent implantation, potential tiny intracranial artery aneurysm, transient blood pressure elevation and the effect of haperanization may be the major factors which induced the intracranial hemorrhage instead of interventional manipulation. The patient had hypertensive history and severe renal artery stenosis, so the lesson from this case suggests that controlling blood pressure before intervention might have avoided this kind of complication. In addition, this group of patients' data showed that no procedural intracranial embolic event occured even distal protection device was unavailable during the first few years. We believe that using the low profile devices like coronary guidewire and balloon before stenting, and applying coronary techniques in CAS may play a very important role in minimizing the distal emboli even though it may not be a strong evidence to draw a conclusion due to the small size of the sample. Furthermore, the follow-up study showed that there was no restenosis in the carotid duplex ultrasound examination 6 months later. CAS has a low restenosis rate and excellent clinical long-term outcome. Future directions in carotid stenting technologies include training and proficiency, quality assessment and improvement, new devices and new trials.11 Such developments would define the role of CAS in treating carotid stenosis, regardless of coexistent coronary artery disease.